Synthesis and Radiolabelling of DOTA-Linked Glutamine Analogues with ~(67,68)Ga as Markers for Increased Glutamine Metabolism in Tumour Cells

摘要

DOTA-linked glutamine analogues with a C6- alkyl and polyethyleneglycol (PEG) chain between the chelating group and the L-glutamine moiety were synthesised and labelled with ~(67,68)Ga using established methods. High yields were achieved for the radiolabelling of the molecules with both radionuclides (>90%), although conversion of the commercially available ~(67)Ga-citrate to the chloride species was a requirement for consistent high radiochemical yields. The generator produced ~(68)Ga was in the [~(68)Ga(OH)4]? form. The ~(67)Ga complexes and the ~(67)Ga complexes were demonstrated to be stable in PBS buffer for a week. Uptake studies were performed with longer lived ~(67)Ga analogues against four tumour cell lines, as well as uptake inhibition studies against L-glutamine, and two known amino acid transporter inhibitors. Marginal uptake was exhibited in the PEG variant radio-complex, and inhibition studies indicate this uptake is via a non-targeted amino acid pathway.